Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial.

BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

A population-based analysis of the management of symptoms of depression among patients with stage IV non-small cell lung cancer (NSCLC) in Ontario, Canada.

PURPOSE: Patients with lung cancer can experience significant psychological morbidities including depression. We characterize patterns and factors associated with interventions for symptoms of depression in stage IV non-small cell lung cancer (NSCLC). METHODS: We conducted a population-based cohort study using health services administrative data in Ontario, Canada of stage IV NSCLC diagnosed from January 2007 to September 2018. A positive symptom of depression score was defined by reporting at least one ESAS (Edmonton Symptom Assessment System) depression score ≥ 2 following diagnosis until the end of follow-up (September 2019). Patient factors included age, sex, comorbidity burden, rurality of residence, and neighbourhood income quintile. Interventions included psychiatry assessment, psychology referral, social work referral and anti-depressant medical therapy (for patients ≥ 65 years with universal drug coverage). Multivariable modified Poisson regression models were used to examine the association between patient factors and intervention use for patients who reported symptoms of depression. RESULTS: In the cohort of 13,159 patients with stage IV NSCLC lung cancer, symptoms of depression were prevalent (71.4%, n = 9,397). Patients who reported symptoms of depression were more likely to receive psychiatry assessment/psychology referral (7.8% vs 3.5%; SD [standardized difference] 0.19), social work referral (17.4% vs 11.9%; SD 0.16) and anti-depressant prescriptions (23.8% vs 13.8%; SD 0.26) when compared to patients who did not report symptoms of depression respectively. In multivariable analyses, older patients were less likely to receive any intervention. Females were more likely to obtain a psychiatry assessment/psychology referral or social work referral. In addition, patients from non-major urban or rural residences were less likely to receive psychiatry assessment/psychology referral or social work referral, however patients from rural residences were more likely to be prescribed anti-depressants. CONCLUSIONS: There is high prevalence of symptoms of depression in stage IV NSCLC. We identify patient populations, including older patients and rural patients, who are less likely to receive interventions that will help identifying and screening for symptoms of depression.

Stereotactic ablative radiotherapy before resection to avoid delay for early-stage lung cancer or oligometastases during the COVID-19 pandemic: Pathologic outcomes from the SABR-BRIDGE protocol.

BACKGROUND: During coronavirus disease 2019 (COVID-19)-related operating room closures, some multidisciplinary thoracic oncology teams adopted a paradigm of stereotactic ablative radiotherapy (SABR) as a bridge to surgery, an approach called SABR-BRIDGE. This study presents the preliminary surgical and pathological results. METHODS: Eligible participants from four institutions (three in Canada and one in the United States) had early-stage presumed or biopsy-proven lung malignancy that would normally be surgically resected. SABR was delivered using standard institutional guidelines, with surgery >3 months following SABR with standardized pathologic assessment. Pathological complete response (pCR) was defined as absence of viable cancer. Major pathologic response (MPR) was defined as ≤10% viable tissue. RESULTS: Seventy-two patients underwent SABR. Most common SABR regimens were 34 Gy/1 (29%, n = 21), 48 Gy/3-4 (26%, n = 19), and 50/55 Gy/5 (22%, n = 16). SABR was well-tolerated, with one grade 5 toxicity (death 10 days after SABR with COVID-19) and five grade 2-3 toxicities. Following SABR, 26 patients underwent resection thus far (13 pending surgery). Median time-to-surgery was 4.5 months post-SABR (range, 2-17.5 months). Surgery was reported as being more difficult because of SABR in 38% (n = 10) of cases. Thirteen patients (50%) had pCR and 19 (73%) had MPR. Rates of pCR trended higher in patients operated on at earlier time points (75% if within 3 months, 50% if 3-6 months, and 33% if ≥6 months; p = .069). In the exploratory best-case scenario analysis, pCR rate does not exceed 82%. CONCLUSIONS: The SABR-BRIDGE approach allowed for delivery of treatment during a period of operating room closure and was well-tolerated. Even in the best-case scenario, pCR rate does not exceed 82%.

Long-term Functional Outcomes Among Older Adults Undergoing Video-assisted Versus Open Surgery for Lung Cancer: A Population-based Cohort Study.

OBJECTIVE: To examine the long-term healthcare dependency outcomes of older adults undergoing VATS compared to open lung cancer resection. SUMMARY OF BACKGROUND DATA: Although the benefits of VATS for lung cancer resection have been reported, there is a knowledge gap related to long-term functional outcomes central to decision-making for older adults. METHODS: We conducted a population-based retrospective comparative cohort study of patients ≥70 years old undergoing lung cancer resection between 2010 and 2017 using linked administrative health databases. VATS was compared to open surgery for lung cancer resection. Outcomes were receipt of homecare and high time-at-home, defined as <14 institution-days within 1 year, in 5 years after surgery. We used time-to-event analyses. Homecare was analyzed as recurrent dichotomous outcome with Andersen-Gill multivariable models, and high time-at-home with Cox multivariable models. RESULTS: Of 4974 patients, 2951 had VATS (59.3%). In the first three months postoperatively, homecare use ranged from 17.5% to 34.4% for VATS and 23.0% to 36.6% for open surgery. VATS was independently associated with lower need for postoperative homecare over 5 years (hazard ratio 0.82, 95% confidence interval 0.74-0.92). 1- and 5-year probability of high "time-at-home" were superior for VATS (74.4% vs 66.7% and 55.6% vs 45.4%, p < 0.001). VATS was independently associated with higher probability of high "time-at-home" (hazard ratio 0.81, 95% confidence interval 0.74-0.89) compared to open surgery. CONCLUSIONS: Compared to open surgery, VATS was associated with lower homecare needs and higher probability of high "time-at-home," indicating reduced long-term functional dependence. Those important patient-centered endpoints reflect the overall long-term treatment burden on mortality and morbidity that can inform surgical decision-making.

Long-term Dependency in Older Adults After Surgery or Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer.

OBJECTIVE: To examine long-term healthcare dependency outcomes of stereotactic body radiation therapy (SBRT) to surgery for older adults with stage I non-small cell lung cancer (NSCLC). BACKGROUND: SBRT is an emerging alternative to surgery in patients with early-stage lung cancer. There remains a paucity of prospective studies comparing these modalities, especially with respect to long-term dependency outcomes in older adults with lung cancer. METHODS: Adults 70 years old and above with stage I NSCLC treated with surgery or SBRT from January 2010 to December 2017 were analyzed using 1:1 propensity score matching. Homecare use, days at home, and time spent alive and at home were compared. E-value methods assessed residual confounding. RESULTS: A total of 1129 and 2570 patients underwent SBRT and surgery, respectively. In all, 1016 per group were matched. SBRT was associated with a higher overall risk of homecare utilization [hazard ratio (HR)=1.75, 95% confidence interval (CI): 1.37-2.23] than surgery up to 5 years following treatment. While the hazards of death or nursing home admission were lower in the first 3 months after SBRT (HR=0.55, 95% CI: 0.36-0.85), they became consistently higher beyond this period and remained high up to 5 years compared with surgery (HR=2.13; 95% CI: 1.85-2.45). The above findings persisted in stratified analyses for frail patients and those with no pretreatment homecare. E-values indicated it was unlikely that the observed estimates could be explained by unmeasured confounders. CONCLUSIONS: Surgery offers robust long-term dependency outcomes compared with SBRT. These are important patient-centered endpoints which may be used for counseling and shared decision-making in older adults with stage I NSCLC.

Symptom Assessment Following Surgery for Lung Cancer: A Canadian Population-based Retrospective Cohort Study.

OBJECTIVE: To conduct a population-level analysis of temporal trends and risk factors for high symptom burden in patients receiving surgery for non-small cell lung cancer (NSCLC). BACKGROUND: A population-level overview of symptoms after curative intent surgery is necessary to inform decision making and supportive care for patients with lung cancer. METHODS: Retrospective cohort study of patients receiving surgery for stages I to III NSCLC between January 2007 and September 2018. Prospectively collection Edmonton Symptom Assessment System (ESAS) scores, linked to provincial administrative data, were used to describe the prevalence, trajectory, and predictors of moderate-to-severe symptoms in the year following surgery. RESULTS: A total of 5350 patients, with 28,490 unique ESAS assessments, were included in the analysis. Moderate-to-severe tiredness (68%), poor wellbeing (63%), and shortness of breath (60%) were the most common symptoms reported. The rise and fall in the proportion of patients experiencing moderate-to-severe symptoms after surgery coincided with the median time to first (58 days, interquartile range: 47-72) and last cycle of chemotherapy (140 days, interquartile range: 118-168), respectively. There was eventual stabilization, albeit above the preoperative baseline, within 6 to 7 months after surgery. Female sex (relative risk [RR] 1.09- 1.26), lower income (RR 1.08-1.23), stage III disease (RR 1.15-1.43), adjuvant therapy (RR 1.09-1.42), chemotherapy within 2 weeks of an ESAS assessment (RR 1.14-1.73), and pneumonectomy (RR 1.05-1.15) were associated with moderate-to-severe symptoms following surgery. CONCLUSIONS: Knowledge of population-level prevalence, trajectory, and predictors of moderate-to-severe symptoms after surgery for NSCLC can be used to facilitate shared decision making and improve symptom management throughout the course of illness.

Variation in Anesthesiology Provider-Volume for Complex Gastrointestinal Cancer Surgery: A Population-Based Study.

OBJECTIVE: Examine between-hospital and between-anesthesiologist variation in anesthesiology provider-volume (PV) and delivery of high-volume anesthesiology care. BACKGROUND: Better outcomes for anesthesiologists with higher PV of complex gastrointestinal cancer surgery have been reported. The factors linking anesthesiology practice and organization to volume are unknown. METHODS: We identified patients undergoing elective esophagectomy, hepatectomy, and pancreatectomy using linked administrative health data sets (2007-2018). Anesthesiology PV was the annual number of procedures done by the primary anesthesiologist in the 2 years before the index surgery. High-volume anesthesiology was PV>6 procedures/year. Funnel plots to described variation in anesthesiology PV and delivery of high-volume care. Hierarchical regression models examined between-anesthesiologist and between-hospital variation in delivery of high-volume care use with variance partition coefficients (VPCs) and median odds ratios (MORs). RESULTS: Among 7893 patients cared for at 17 hospitals, funnel plots showed variation in anesthesiology PV (median ranging from 1.5, interquartile range: 1-2 to 11.5, interquartile range: 8-16) and delivery of HV care (ranging from 0% to 87%) across hospitals. After adjustment, 32% (VPC 0.32) and 16% (VPC: 0.16) of the variation were attributable to between-anesthesiologist and between-hospital differences, respectively. This translated to an anesthesiologist MOR of 4.81 (95% CI, 3.27-10.3) and hospital MOR of 3.04 (95% CI, 2.14-7.77). CONCLUSIONS: Substantial variation in anesthesiology PV and delivery of high-volume anesthesiology care existed across hospitals. The anesthesiologist and the hospital were key determinants of the variation in high-volume anesthesiology care delivery. This suggests that targeting anesthesiology structures of care could reduce variation and improve delivery of high-volume anesthesiology care.

The Association Between Hospital High-volume Anesthesiology Care and Patient Outcomes for Complex Gastrointestinal Cancer Surgery: A Population-based Study.

OBJECTIVE: To examine the association of between hospital rates of high-volume anesthesiology care and of postoperative major morbidity. BACKGROUND: Individual anesthesiology volume has been associated with individual patient outcomes for complex gastrointestinal cancer surgery. However, whether hospital-level anesthesiology care, where changes can be made, influences the outcomes of patients cared at this hospital is unknown. METHODS: We conducted a population-based retrospective cohort study of adults undergoing esophagectomy, pancreatectomy, or hepatectomy for cancer from 2007 to 2018. The exposure was hospital-level adjusted rate of high-volume anesthesiology care. The outcome was hospital-level adjusted rate of 90-day major morbidity (Clavien-Dindo grade 3-5). Scatterplots visualized the relationship between each hospital's adjusted rates of high-volume anesthesiology and major morbidity. Analyses at the hospital-year level examined the association with multivariable Poisson regression. RESULTS: For 7893 patients at 17 hospitals, the rates of high-volume anesthesiology varied from 0% to 87.6%, and of major morbidity from 38.2% to 45.4%. The scatter plot revealed a weak inverse relationship between hospital rates of high-volume anesthesiology and of major morbidity (Pearson: -0.23). The adjusted hospital rate of high-volume anesthesiology was independently associated with the adjusted hospital rate of major morbidity (rate ratio: 0.96; 95% CI, 0.95-0.98; P <0.001 for each 10% increase in the high-volume rate). CONCLUSIONS: Hospitals that provided high-volume anesthesiology care to a higher proportion of patients were associated with lower rates of 90-day major morbidity. For each additional 10% patients receiving care by a high-volume anesthesiologist at a given hospital, there was an associated reduction of 4% in that hospital's rate of major morbidity.

Rationale and design of the colchicine for the prevention of perioperative atrial fibrillation in patients undergoing major noncardiac thoracic surgery (COP-AF) trial.

BACKGROUND: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery. METHODS AND RESULTS: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (eg, severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The 2 independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the 2 co-primary outcomes. The COP-AF main results are expected in 2023. CONCLUSIONS: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery.

Temporal and Spatial Patterns of Inflammation and Tissue Injury in Patients with Postoperative Respiratory Failure after Lung Resection Surgery: A Nested Case-Control Study.

Thoracic surgeries involving resection of lung tissue pose a risk of severe postoperative pulmonary complications, including acute respiratory distress syndrome (ARDS) and respiratory failure. Lung resections require one-lung ventilation (OLV) and, thus, are at higher risk of ventilator-induced lung injury (VILI) attributable to barotrauma and volutrauma in the one ventilated lung, as well as hypoxemia and reperfusion injury on the operated lung. Further, we also aimed to assess the differences in localized and systemic markers of tissue injury/inflammation in those who developed respiratory failure after lung surgery versus matched controls who did not develop respiratory failure. We aimed to assess the different inflammatory/injury marker patterns induced in the operated and ventilated lung and how this compared to the systemic circulating inflammatory/injury marker pattern. A case-control study nested within a prospective cohort study was performed. Patients with postoperative respiratory failure after lung surgery (n = 5) were matched with control patients (n = 6) who did not develop postoperative respiratory failure. Biospecimens (arterial plasma, bronchoalveolar lavage separately from ventilated and operated lungs) were obtained from patients undergoing lung surgery at two timepoints: (1) just prior to initiation of OLV and (2) after lung resection was completed and OLV stopped. Multiplex electrochemiluminescent immunoassays were performed for these biospecimen. We quantified 50 protein biomarkers of inflammation and tissue injury and identified significant differences between those who did and did not develop postoperative respiratory failure. The three biospecimen types also display unique biomarker patterns.

The profibrotic and senescence phenotype of old lung fibroblasts is reversed or ameliorated by genetic and pharmacological manipulation of Slc7a11 expression.

Increased senescence and expression of profibrotic genes in old lung fibroblasts contribute to disrepair responses. We reported that primary lung fibroblasts from old mice have lower expression and activity of the cystine transporter Slc7a11/xCT than cells from young mice, resulting in changes in both the intracellular and extracellular redox environments. This study examines the hypothesis that low Slc7a11 expression in old lung fibroblasts promotes senescence and profibrotic gene expression. The levels of mRNA and protein of Slc7a11, senescence markers, and profibrotic genes were measured in primary fibroblasts from the lungs of old (24 mo) and young (3 mo) mice. In addition, the effects of genetic and pharmacological manipulation of Slc7a11 were investigated. We found that decreased expression of Slc7a11 in old cells was associated with elevated markers of senescence (p21, p16, p53, and ß-galactosidase) and increased expression of profibrotic genes (Tgfb1, Smad3, Acta2, Fn1, Col1a1, and Col5a1). Silencing of Slc7a11 in young cells replicated the aging phenotype, whereas overexpression of Slc7a11 in old cells decreased expression of senescence and profibrotic genes. Young cells were induced to express the senescence and profibrotic phenotype by sulfasalazine, a Slc7a11 inhibitor, whereas treatment of old cells with sulforaphane, a Slc7a11 inducer, decreased senescence without affecting profibrotic genes. Like aging cells, idiopathic pulmonary fibrosis fibroblasts show decreased Slc7a11 expression and increased profibrotic markers. In short, old lung fibroblasts manifest a profibrotic and senescence phenotype that is modulated by genetic or pharmacological manipulation of Slc7a11.

Province-Wide Analysis of Patient-Reported Outcomes for Stage IV Non-Small Cell Lung Cancer.

BACKGROUND: In Ontario, Canada, patient-reported outcome (PRO) evaluation through the Edmonton Symptom Assessment System (ESAS) has been integrated into clinical workflow since 2007. As stage IV non-small cell lung cancer (NSCLC) is associated with substantial disease and treatment-related morbidity, this province-wide study investigated moderate to severe symptom burden in this population. MATERIALS AND METHODS: ESAS collected from patients with stage IV NSCLC diagnosed between 2007 and 2018 linked to the Ontario provincial health care system database were studied. ESAS acquired within 12 months following diagnosis were analyzed and the proportion reporting moderate to severe scores (ESAS ≥4) in each domain was calculated. Predictors of moderate to severe scores were identified using multivariable Poisson regression models with robust error variance. RESULTS: Of 22,799 patients, 13,289 (58.3%) completed ESAS (84,373 assessments) in the year following diagnosis. Patients with older age, with high comorbidity, and not receiving active cancer therapy had lower ESAS completion. The majority (94.4%) reported at least one moderate to severe symptom. The most prevalent were tiredness (84.1%), low well-being (80.7%), low appetite (71.7%), and shortness of breath (67.8%). Most symptoms peaked at diagnosis and, while declining, remained high in the following year. On multivariable analyses, comorbidity, low income, nonimmigrants, and urban residency were associated with moderate to severe symptoms. Moderate to severe scores in all ESAS domains aside from anxiety were associated with radiotherapy within 2 weeks prior, whereas drowsiness, low appetite and well-being, nausea, and tiredness were associated with systemic therapy within 2 weeks prior. CONCLUSION: This province-wide PRO analysis showed moderate to severe symptoms were prevalent and persistent among patients with metastatic NSCLC, underscoring the need to address supportive measures in this population especially around treatments. IMPLICATIONS FOR PRACTICE: In this largest study of lung cancer patient-reported outcomes (PROs), stage IV non-small cell lung cancer patients had worse moderate-to-severe symptoms than other metastatic malignancies such as breast or gastrointestinal cancers when assessed with similar methodology. Prevalence of moderate-to-severe symptoms peaked early and remained high during the first year of follow-up. Symptom burden was associated with recent radiation and systemic treatments. Early and sustained PRO collection is important to detect actionable symptom progression, especially around treatments. Vulnerable patients (e.g., older, high comorbidity) who face barriers in attending in-person clinic visits had lower PRO completion. Virtual PRO collection may improve completion.

Allergen inhalation generates pro-inflammatory oxidised phosphatidylcholine associated with airway dysfunction.

Oxidised phosphatidylcholines (OxPCs) are produced under conditions of elevated oxidative stress and can contribute to human disease pathobiology. However, their role in allergic asthma is unexplored. The aim of this study was to characterise the OxPC profile in the airways after allergen challenge of people with airway hyperresponsiveness (AHR) or mild asthma. The capacity of OxPCs to contribute to pathobiology associated with asthma was also to be determined.Using bronchoalveolar lavage fluid from two human cohorts, OxPC species were quantified using ultra-high performance liquid chromatography-tandem mass spectrometry. Murine thin-cut lung slices were used to measure airway narrowing caused by OxPCs. Human airway smooth muscle (HASM) cells were exposed to OxPCs to assess concentration-associated changes in inflammatory phenotype and activation of signalling networks.OxPC profiles in the airways were different between people with and without AHR and correlated with methacholine responsiveness. Exposing patients with mild asthma to allergens produced unique OxPC signatures that associated with the severity of the late asthma response. OxPCs dose-dependently induced 15% airway narrowing in murine thin-cut lung slices. In HASM cells, OxPCs dose-dependently increased the biosynthesis of cyclooxygenase-2, interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor and the production of oxylipins via protein kinase C-dependent pathways.Data from human cohorts and primary HASM cell culture show that OxPCs are present in the airways, increase after allergen challenge and correlate with metrics of airway dysfunction. Furthermore, OxPCs may contribute to asthma pathobiology by promoting airway narrowing and inducing a pro-inflammatory phenotype and contraction of airway smooth muscle. OxPCs represent a potential novel target for treating oxidative stress-associated pathobiology in asthma.

Patient-reported symptoms following diagnosis in esophagus cancer patients treated with palliative intent.

The majority of patients with esophagus cancer have advanced-stage disease without curative options. For these patients, treatment is focused on improving symptoms and quality of life. Despite this, little work has been done to quantify symptom burden for incurable patients. We describe symptoms using the Edmonton Symptom Assessment System (ESAS) among esophagus cancer patients treated for incurable disease. This retrospective cohort study linked administrative datasets to prospectively collected ESAS data of non-curatively treated adult esophagus cancer patients diagnosed between January 1, 2009 and September 30, 2016. ESAS measures nine common cancer-related symptoms: anxiety, depression, drowsiness, lack of appetite, nausea, pain, shortness of breath, tiredness, and impaired well-being. Frequency of severe symptoms (score ≥ 7/10) was described by month for the 6 months from diagnosis for all patients and by treatment type (chemotherapy alone, radiotherapy alone, both chemotherapy and radiotherapy, and best supportive care). A sensitivity analysis limited to patients who survived at least 6 months was performed to assess robustness of the results to proximity to death and resulting variation in follow-up time. Among 2,989 esophagus cancer patients diagnosed during the study period and meeting inclusion criteria, 2,103 reported at least one ESAS assessment in the 6 months following diagnosis and comprised the final cohort. Patients reported a median of three (IQR 2-7) ESAS assessments in the study period. Median survival was 7.6 (IQR 4.1-13.7) months. Severe lack of appetite (53.1%), tiredness (51.1%), and impaired well-being (42.7%) were the most commonly reported symptoms. Severe symptoms persisted throughout the 6 months after the diagnosis. Subgroup analysis by treatment showed no worsening of symptoms over time in those treated by either chemotherapy alone, or both chemotherapy and radiation. Results followed a similar pattern on sensitivity analysis. Patients diagnosed with incurable esophagus cancer experience considerable symptom burden in the first 6 months after diagnosis and the frequency of severe symptoms remains high throughout this period. Patients with this disease require early palliative care and psychosocial support upon diagnosis and support throughout the course of their cancer journey.

The Potential Dangers of Recruitment Maneuvers During One Lung Ventilation Surgery.

BACKGROUND: Existing evidence regarding lung-protective ventilation (LPV) during one-lung ventilation (OLV) focuses on surrogate outcomes. Our objective was to assess whether an LPV protocol during OLV surgery is associated with reduced respiratory complications. MATERIALS AND METHODS: This was a matched control retrospective cohort study of patients undergoing pulmonary resection at a tertiary Canadian hospital. The experimental group (n = 50) was derived from primary data of two crossover RCTs, which utilized protocolized LPV strategies with varying levels of positive end-expiratory pressure and recruitment maneuvers. The control group was drawn from a prospectively maintained database; these patients received conventional nonprotocolized ventilation (2000-2010). Each experimental group patient was matched 1:1 with a control group patient with respect to clinically relevant variables (age, sex, diagnosis, smoking status, cardiovascular disease status, comorbidity, BMI, preoperative forced expiratory volume in 1 s, surgery type). Major respiratory complications were defined as composite of acute respiratory distress syndrome, need for new positive-pressure ventilation, and atelectasis requiring bronchoscopy. Paired and unpaired statistical tests were used. RESULTS: Patients appeared well matched. Major respiratory complications occurred in 8% (n = 4) and 2% (n = 1) of patients in experimental and control groups, respectively (P = 0.50). There was a trend toward increased mortality (4 versus 0, P = 0.06) with protocolized LPV. The patients who died had respiratory complications; one had acute respiratory distress syndrome and two had profound hypoxemia. CONCLUSIONS: There was a nonsignificant trend toward increased mortality with LPV during OLV. Although limited by a small sample size, our findings identify a potential danger to excessive recruitment maneuvers. Larger studies, with clinically important outcomes are needed to better define the risk/benefit trade-offs for LPV during OLV.

Frailty assessment prior to thoracic surgery for lung or esophageal cancer: a feasibility study.

BACKGROUND: Frailty assessment has not been thoroughly assessed in thoracic surgery. Our primary objective was to assess the feasibility of comprehensive frailty testing prior to lung and esophageal surgery for cancer. The secondary objective was to assess the utility of frailty indices in risk assessment prior to thoracic surgery. METHODS: Prospectively recruited patients completed multiple physiotherapy tests (6-min walk, gait speed, hand-grip strength), risk stratification (Charlson Comorbidity Index, Revised Cardiac Risk Index, Modified Frailty Index), and quality of life questionnaires. Lean psoas area was also assessed by a radiologist using positron emission tomography/computed tomography scans. Data was analyzed using Fisher's exact, Mann-Whitney U and independent t tests. RESULTS: The feasibility of comprehensive frailty assessment was assessed over a 4-month period among 40 patients (esophagus n = 20; lung n = 20). Risk stratification questionnaires administered in clinic had 100% completion rates. Physiotherapy testing required a trained physiotherapist and an additional visit to the pre-admission clinic; these tests proved difficult to coordinate and had lower completion rates (63-75%). Although most measures were not significantly associated with occurrence of complications, the Modified Frailty Index approached statistical significance (p = 0.06). CONCLUSIONS: Frailty assessment is feasible in the pre-operative outpatient setting and had a high degree of acceptance among surgeons and patients. Of the risk stratification questionnaires, the Modified Frailty Index may be useful in predicting outcomes as per this feasibility study. Pre-operative frailty assessment can identify vulnerable oncology patients to aid in treatment planning with the goal of optimizing clinical outcomes and resource allocation.

Is tissue still the issue? Lobectomy for suspicious lung nodules without confirmation of malignancy.

BACKGROUND: Histologic confirmation of malignancy has been indicated for a suspicious lung nodule prior to resection. The purpose of this study was to determine whether or not foregoing routine tissue biopsy increased the incidence of lobectomy for benign lesions. METHODS: Retrospective cohort of 256 patients who underwent thoracoscopic or open lobectomy for a confirmed or suspected pulmonary malignancy, with or without tissue diagnosis. Clinical, radiographic, and pathologic data were compared. RESULTS: Among 256 patients, 127 had attempted biopsy (group A) and 129 had no biopsy procedure (group B). There was no significant difference in the incidence of benign resections between the groups (Group A = 4 (3.2%) benign pathology vs group B = 9 (7.0%; P = 0.16). Group B had significantly lower operative time (127.1 vs 112.3 minutes; P = 0.004) and intraoperative complications (23 vs 37 patients; P = 0.03). There was a trend toward longer hospital stay and surgical waiting time in group A (6.6 vs 5.2 days, P = 0.24; 92.4 vs 66.2 days; P = 0.14, respectively). CONCLUSION: Foregoing biopsies and proceeding to lobectomy in selected patients with suspicious lung nodules is safe, did not increase the incidence of resected benign pathology, and may decrease surgical wait time. Patients should be carefully evaluated and counseled.

RBC transfusion is associated with increased risk of respiratory failure after pneumonectomy.

BACKGROUND AND OBJECTIVES: Pneumonectomy is associated with high risk of respiratory complications. Our objective was to determine if transfusions are associated with increased rate of ARDS and respiratory failure in adults undergoing elective pneumonectomy. METHODS: Retrospective cohort study of consecutive pneumonectomies undertaken at a tertiary hospital (2003-2013). Multivariable logistic regression was performed to adjust for confounding factors. RESULTS: ARDS and respiratory failure occurred in 12.4% (n = 20) and 19.2% (n = 31) of 161 pneumonectomy patients, respectively, and were more likely to occur in transfused patients (P = 0.03, P < 0.001). pRBCs, FFP and platelets were transfused in 27% (n = 43), 6% (n = 9), and 2% (n = 3), respectively. On multivariable analyses utilizing blood products as continuous and binary variables, pRBC use was the only independent predictor of ARDS with odds ratio (OR) = 1.23 (95%CI:1.08-1.39, P = 0.002) and OR = 2.45 (95%CI:1.10-5.49, P = 0.03), respectively. On multivariable analyses utilizing blood products as continuous and binary variables, pRBCs were the only independent predictor of respiratory failure with OR = 1.37 (95%CI:1.16-1.60, P < 0.001) and OR = 3.17 (95%CI:1.25-8.02, P = 0.02), respectively. CONCLUSIONS: Peri-operative pRBC use appears to be an independent risk factor for ARDS and respiratory failure after pneumonectomy. There is a significant dose-response relationship. Platelets and FFP did not appear to increase ARDS risk but this may be due to low utilization.

Association between Prehospital Time and Mortality following Blunt Thoracic Aortic Injuries.

BACKGROUND: Blunt thoracic aortic injuries (BTAIs) can be lethal, but advances in trauma systems and surgical care have helped reduce mortality. The purpose of this study is to investigate whether time from injury to presentation is associated with mortality following BTAI. METHODS: Using the Ontario Trauma Registry, all patients were identified who were hospitalized with BTAI between 1999 and 2009. Variables including age, sex, Injury Severity Score, Charlson comorbidity index, systolic blood pressure on admission, operative intervention, and time from injury to presentation were analyzed using multivariate logistic regression to determine independent predictors of mortality. RESULTS: We identified 264 cases of BTAI that survived until hospital admission. Of these, 220 patients had documented time from injury to presentation to hospital. Most, 68.2% (n = 150), presented within 60 min of injury. On adjusted multivariate analysis, a prehospital time of ≤60 min independently predicted higher mortality (odds ratio 0.27, 95% confidence interval 0.08-0.89, P = 0.03). Tight clustering was seen with prehospital time and mortality. CONCLUSIONS: Rather than reducing mortality as hypothesized, a shorter time between BTAI and hospital presentation (<60 min) is associated with increased mortality. This may be the result of selection bias with the quicker transport of more severely injured patients.